This program combines the technologies of protein structural and physical chemistry, cell biology, molecular biology and genetics, and clinical investigation to elucidate the contributions of bone proteins to bone structure/function. The integrated program aims at identifying and characterizing bone proteins. This knowledge will be utilized in three fashions: 1) to provide tools to identify cells involved in bone synthesis and to prove their regulation at both the protein and nucleic acid level. 2) to develop an appreciation of the contribution of collagenous and noncollagenous proteins in providing the structural/functional qualities of bone. 3) to evaluate the utility of knowledge of the blood and urine levels of bone proteins and their fragments in the evaluation of normal and abnormal skeletal function. The research program proposed brings together experienced laboratories directed by seasoned investigators who have demonstrated ability to work together. It is hoped the concerted research effort will provide fundamental insights into bone biology and also the technology to combat osteoporosis and other major diseases of bone formation.